Physiology of the vasculature 2 Flashcards
Diseases to target that are caused by endothelial dysfunction?
- Pulmonary arterial hypertension
- Angina
- Raynaud’s
- Heart failure
- Hypertension
What is heart failure characterised by?
Inadequate CO to meet the metabolic demands of the body
Secondary disease to coronary heart failure, atherosclerosis and myocardial infarction
Heart is permanently damaged!
What is PAH characterised by?
Narrowed pulmonary vessels
Poor gas exchange at the lung
Increased right heart pressure
High rates of morbidity
What is angina characterised by?
Insufficient O2 supply to cardiac tissue during exercise, secondary to coronary heart disease
Narrowing of vessels due to formation of plaques
Results in chest pain
What is Raynauds characterised by?
Too much vasoconstriction of the small arteries and arteriole vessels. Results in white/blue fingers, gangreen, ulceration in extreme cases, white fingers, can be secondary to smoking
Wear warm clothes!!!
What is Hypertension characterised by?
Secondary to atherosclerosis, loss of the glycocalyx, calcification, decreased NO, loss of elastin and fluid retention.
Results in breathlessness, fatigue and HBP!!! Leading risk factor in global disease burden
How is the vasculature involved in these diseases?
Ecs produce vasoactive factors that regulate contraction of blood vessels
Activated or disease ECs increase production of contractile mediators which can result in the diseases seen
Mediators of smooth muscle relaxation ?
cGMP, cAMP, K+ channels!!!
Endothelial derived prostanoids - names and where they exert action?
Thromboxane A2 - increases production of IP3 which induces release of Ca2+ from the SR
Prostoglandin A2 - impact depends on the GPCR it binds to at various areas of blood vessels
Prostoglandin I2 - increase relaxation by increasing cAMP production
Different forms of NO
Nitroglycerine - common angina production - causes rapid production of NO
Sodium Nitroprusside - rapid delivery, treatment for emergency hypertension, IV injectable
Inhaled NO - used in critical conditions to induce vasodilation in severe pulmonary hypertension
Endothelial derived endothelin – mechanism of action?
Bind to ETa/ETb receptors to cause contraction of SMCs, stimulating IP3 production and inducing release of Ca2+ from the SR
What is Bosentan? what is ECE?
BOSENTAN - ET receptor antagonist - treatment for PH, prevents contraction by ET induced mechanism
ECE - converts big endothelin to ET-1 - can block this enzyme as a therapeutic target to treat hypertension
Prostanoid treatment - types and mechanisms?
Corticosteroids - supress prostoglandin formation
Iloprost - PGI2 analogue
Epoprostanol - IP receptor agonist - stimulates relaxation in same way as PGI2
Enalapril - what is it and what are its side effects?
ACE—| , used to treat hypertension, HF and MIs. Enalapril is longer lasting than others as once in the body it is converted to an active metabolite (PRO DRUG)
Side effects – hypotension, cough, urea in protein, change in taste buds
Angiotensin I antagonists – examples and useful in combo with what?
Sartans, cause a decrease in BP, useful in combo with ACE inhibitors!
